Magnetic resonance imaging 3t and total fibrotic volume in autosomal dominant polycystic kidney disease

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the most common renal hereditary disorder. Several authors have attempted to identify a kidney damage marker for predicting the prognosis and the effectiveness of therapy in ADPKD. The aim of this study was to identify and quantify in ADPKD, through a novel MR protocol with 3 Tesla (MRI 3Tesla), the presence of parenchymal fibrotic tissue at early stage of disease, able to correlate the glomerular filtrate and to predict the loss of the function renal. MATERIAL AND METHODS: 15 ADPKD patients undergone to renal MRI 3Tesla at T0 and revaluated after follow up (T1) of 5 years. We have evaluated renal function, plasma aldosterone concentration (PAC), insulin resistance and surrogate markers of atherosclerosis (carotid intima media thickness (IMT), ankle/brachial index (ABI) and left ventricular mass index (LVMI). RESULTS: Our study showed a significant negative correlation between total kidney volume and estimated glomerular filtration rate (eGFR) during observational observation (p<0.02). Moreover, we showed a negative correlation between eGFR with Total Fibrotic Volume (TFV) (p<0.04) and Total Perfusion Volume/Total kidney Volume(<0.02). Moreover TFV was correlated positively with PAC (p<0.05), insulin values (p<0.05), ABI (p <0.05) and LVMI(p<0.01). CONCLUSIONS: The MRI 3Tesla, despite the high costs, could be considered an useful and non-invasive method in the evaluation of fibrotic tissue and progression of the disease in ADPKD patients. Further clinical trials on larger group are due to confirm the results of this pilot study, suggesting that MRI 3Tesla can be useful to evaluate the effectiveness of new therapeutic strategies. This article is protected by copyright. All rights reserved

Discontinuously supervised aerobic training vs. physical activity promotion in the self-management of type 2 diabetes in older Italian patients: design and methods of the 'TRIPL-A' randomized controlled trial

Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The 'TRIPL-A' study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle

Invasive pleural malignant mesothelioma with rib destruction and concurrent osteosarcoma in a dog

A 7-year-old Dachshund was clinically examined because of a 10-day history of lameness in the left hind limb. On the basis of radiological and cytological findings, an osteosarcoma of the left acetabular region was suspected. The dog underwent a hemipelvectomy and osteosarcoma was diagnosed by subsequent histopathological examination. An immovable subcutaneous mass was noted on the left chest wall during the physical examination and non-septic neutrophilic inflammation was diagnosed by cytology. Forty days later, the dog showed signs of respiratory distress with an in-diameter increase of the subcutaneous mass up to 4 cm. Thoracic radiography and ultrasonography revealed pleural effusion and a lytic process in the fourth left rib. Furthermore, ultrasound examination revealed a mixed echogenic mobile structure with a diameter of around 2 cm floating within the pleural fluid of the left hemithorax close to the pericardium. The dog underwent surgery for an en bloc resection of the subcutaneous mass together with the fourth rib and the parietal pleura. Moreover, the left altered lung lobe, corresponding to the mobile structure detected by ultrasound, was removed. Based on cytological, histopathological, and immunohistochemical examinations, an invasive epithelioid pleural malignant mesothelioma was diagnosed

Two novel PRNP truncating mutations broaden the spectrum of prion amyloidosis

Truncating mutations in PRNP have been associated with heterogeneous phenotypes ranging from chronic diarrhea and neuropathy to dementia, either rapidly or slowly progressive. We identified novel PRNP stop-codon mutations (p.Y163X, p.Y169X) in two Italian kindreds. Disease typically presented in the third or fourth decade with progressive autonomic failure and diarrhea. Moreover, one proband (p.Y163X) developed late cognitive decline, whereas some of his relatives presented with isolated cognitive and psychiatric symptoms. Our results strengthen the link between PRNP truncating mutations and systemic abnormal PrP deposition and support a wider application of PRNP screening to include unsolved cases of familial autonomic neuropathy

Immunohistochemical investigations on Brucella ceti-infected, neurobrucellosis-affected striped dolphins (Stenella coeruleoalba)

Bacteria of the genus Brucella cause brucellosis, an infectious disease common to humans as well as to terrestrial and aquatic mammals. Since 1994 several cases of Brucella spp. infection have been reported in marine mammals worldwide. Indeed, since human brucellosis ranks as one of the most common bacterial zoonotic infections on a global scale, it is necessary to increase our knowledge about it also in the marine environment. Brucella ceti, which is phenotypically similar to other smooth brucellae as B. abortus and B. melitensis, shares with the latter two the same surface antigens that are routinely used for the serological diagnosis of Brucella spp. infection. Marine mammal Brucella spp. infections are characterized by a pathogenicity similar to their terrestrial counterparts, with the occurrence of abortion, stillbirth and orchitis and an involvement of the host’s central nervous system (CNS), similarly to what happens in mankind. While sero-epidemiological data suggest that Brucella spp. infection is widespread globally, detecting Brucella spp.-associated antigens by immunohistochemistry (IHC) in tissues from infected animals is often troublesome. The present study was aimed at investigating, by means of IHC based upon the utilization of an anti-Brucella LPS monoclonal antibody (MAb), the CNS immunoreactivity (IR) shown by B. ceti-infected, neurobrucellosis-affected striped dolphins

Endothelin-1 Inhibits Prolyl Hydroxylase Domain 2 to Activate Hypoxia-Inducible Factor-1α in Melanoma Cells

The endothelin B receptor (ET(B)R) promotes tumorigenesis and melanoma progression through activation by endothelin (ET)-1, thus representing a promising therapeutic target. The stability of hypoxia-inducible factor (HIF)-1alpha is essential for melanomagenesis and progression, and is controlled by site-specific hydroxylation carried out by HIF-prolyl hydroxylase domain (PHD) and subsequent proteosomal degradation.Here we found that in melanoma cells ET-1, ET-2, and ET-3 through ET(B)R, enhance the expression and activity of HIF-1alpha and HIF-2alpha that in turn regulate the expression of vascular endothelial growth factor (VEGF) in response to ETs or hypoxia. Under normoxic conditions, ET-1 controls HIF-alpha stability by inhibiting its degradation, as determined by impaired degradation of a reporter gene containing the HIF-1alpha oxygen-dependent degradation domain encompassing the PHD-targeted prolines. In particular, ETs through ET(B)R markedly decrease PHD2 mRNA and protein levels and promoter activity. In addition, activation of phosphatidylinositol 3-kinase (PI3K)-dependent integrin linked kinase (ILK)-AKT-mammalian target of rapamycin (mTOR) pathway is required for ET(B)R-mediated PHD2 inhibition, HIF-1alpha, HIF-2alpha, and VEGF expression. At functional level, PHD2 knockdown does not further increase ETs-induced in vitro tube formation of endothelial cells and melanoma cell invasiveness, demonstrating that these processes are regulated in a PHD2-dependent manner. In human primary and metastatic melanoma tissues as well as in cell lines, that express high levels of HIF-1alpha, ET(B)R expression is associated with low PHD2 levels. In melanoma xenografts, ET(B)R blockade by ET(B)R antagonist results in a concomitant reduction of tumor growth, angiogenesis, HIF-1alpha, and HIF-2alpha expression, and an increase in PHD2 levels.In this study we identified the underlying mechanism by which ET-1, through the regulation of PHD2, controls HIF-1alpha stability and thereby regulates angiogenesis and melanoma cell invasion. These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Position Paper on Diagnosis, Prognosis and Treatment by the MNGIE International Network

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE) is a rare autosomal recessive disease caused by TYMP mutations and thymidine phosphorylase (TP) deficiency. Thymidine and deoxyuridine accumulate impairing the mitochondrial DNA maintenance and integrity. Clinically, patients show severe and progressive gastrointestinal and neurological manifestations. The onset typically occurs in the second decade of life and mean age at death is 37 years. Signs and symptoms of MNGIE are heterogeneous and confirmatory diagnostic tests are not routinely performed by most laboratories, accounting for common misdiagnosis. Factors predictive of progression and appropriate tests for monitoring are still undefined. Several treatment options showed promising results in restoring the biochemical imbalance of MNGIE. The lack of controlled studies with appropriate follow‐up accounts for the limited evidence informing diagnostic and therapeutic choices. The International Consensus Conference (ICC) on MNGIE, held in Bologna, Italy, on March 30th‐31st, 2019, aimed at an evidence‐based consensus on diagnosis, prognosis and treatment of MNGIE among experts, patients, caregivers and other stakeholders involved in caring the condition. The conference was conducted according to the National Institute of Health Consensus Conference methodology. A consensus development panel formulated a set of statements and proposed a research agenda. Specifically, the ICC produced recommendations on: (1) diagnostic pathway; (2) prognosis and the main predictors of disease progression; (3) efficacy and safety of treatments; and (4) research priorities on diagnosis, prognosis and treatment. The Bologna ICC on diagnosis, management and treatment of MNGIE provided evidence‐based guidance for clinicians incorporating patients' values and preferences

Acque minerali a basso contenuto di sodio: loro utilizzo in alcune patologia

Il sodio riveste un ruolo fondamentale nell’insorgenza di ipertensione arteriosa e nel danno d’organo anche attraverso un effetto ossidativo , mediato dalla produzione di ROS. Studi sperimentali hanno dimostrato che lo stress ossidativo da carico di sale è associato ad ischemia e fibrosi tissutale con disfunzione diastolica del ventricolo sinistro e danno renale cronico .La presenza di uno stress ossidativo a livello del letto vascolare è stato dimostrato in una varietà di ratti sodio-sensibili sottoposti a carico di sale.Una dieta troppo ricca di sodio nei pazienti con insufficienza renale cronica aumenta la vasocostrizione della arteriose glomerulari con conseguente aumento della filtrazione , responsabile dell’evoluzione del danno renale. Una dieta iposodica è elemento fondamentale nella prevenzione e terapia dell’ipertensione arteriosa. Le acque oligominerali iposodiche possono essere considerate in questo senso un supporto nutrizionale importante in particolare nelle situazioni di eccessivo accumulo idrosalino

lA CALCOLOSI RENALE:RUOLO ATTUALE DELLA TERAPIA MEDICA

La calcolosi renale è una patologia gravata da un’alta incidenza di recidiva. La conoscenza delle alterazioni metaboliche alla base delle diverse forme di calcolosi ha permesso di attuare terapie mediche in grado di prevenire la formazione di un nuovo calcolo ma l’eterogeneità etiologica e clinica della malattia rende difficile ottenerne una remissione stabile .La facilità , peraltro , a rimuovere i calcoli con un metodo poco invasivo , quale l’ESWL ha portato a discutere sulla reale utilità di terapie mediche preventive , non prive peraltro di effetti collaterali . In questo lavoro viene discusso il ruolo che la terapia medica ancora oggi riveste e le nuove prospettive terapeutiche alla luce della conoscenza di nuovi meccanismi fisiopatogenetici